Transcript Pharmacologic Debridement: More Does Not Equal Better

Pharmacologic Debridement:
More Does Not Equal Better
Jacob B. Blumenthal, MD, FACP
Baltimore Geriatrics Research, Education and Clinical Center/VAMC
University of Maryland School of Medicine
Baltimore, MD
[email protected]
Nicole J. Brandt, PharmD, CGP, BCPP, FASCP
Peter Lamy Center on Drug Therapy and Aging
University of Maryland, School of Pharmacy
Baltimore, MD
[email protected]
…but…
• Unlike Dick the Butcher
– ”The first thing we do, let's kill all the lawyers”
• Not: medications are bad
– Rather, suggesting need for judicious use and
continuous re-litigation
Henry VI
William Shakespeare
Outline
• Demographics
– Aging and Multimorbidities
– Polypharmacy and ADR’s
• Age-related changes
– Pharmacodynamics (absorption, clearance)
– Body Composition
• What are we doing? Whose standard?
• Bad Drugs: Beer’s List, HEDIS High Risk Meds
• Semper Vigilentes – Med Review as a SOP
The Demographic Imperative
• Population Explosion
– Where we are:
• Over 65 years old: 12.9% of population
• Over 75: 6.1% 18,766,000
>65 years old (millions)
– Where we’re going
100
90
80
70
60
50
40
30
20
10
0
2010 2015 2020 2025 2030 2035 2040 2045 2050
US Census Bureau
Prevalence of Multimorbidities
Arch Intern Med. 2002;162(20):2269-2276.
doi:10.1001/archinte.162.20.2269
…which influence prognosis
Risk for Mortality in Frail Elders
Risks:
Male = 2 points
CHF = 3 points
Age >85 = 3 points
Carey EC et al. JAGS 2008; 56:68–75.
Nonetheless, Demographically…
• Compression of Morbidity
Fries, 1982
The Search for Clinical Decision Making Tools
• Large heterogeneity  difficult to find applicable studies
– “No index…prospectively tested and found to be accurate in a
large diverse sample…no study was completely free from
potential sources of bias. Testing of transportability was
limited, raising concerns about overfitting and underfitting.
These factors limit a clinician's ability to assess the accuracy of
these indices across patient groups that differ according to
severity of illness, methodology of data collection, geographic
location, and time.”
• The Controversy
– How far can we extrapolate data for this population?
– To what extent can we base clinical practice on biologic
plausibility in the absence of clinical trail data?
Importance of Multimorbidity
• Over 50% of older adults have 3+ chronic conditions
• Increased risk of:
– Death
– Institutionalization
– Increased utilization of healthcare resources
– Decreased quality of life
– Higher rates of adverse effects of treatment or
interventions
Brendan Smialowski (NY Times)
• Almost all existing “guidelines” have single disease focus
• Best approaches to decision-making and clinical
management of older adults with multimorbidity remain
unclear
Prevalence of Polypharmacy…
Qato et al JAMA 2008: 300(24): 2867-2878
Treatment Complexity & Feasibility
• Difficult to define a uniform
threshold for treatment complexity
and feasibility
• Influenced by
– Treatment regimen
– Older adult’s unique characteristics
• Barriers to assessing complexity
and feasibility
– Time-consuming
– Lack of necessary training
Drugs are not benign
• ~100,000 emergency hospitalizations/year
due to adverse drug events (ADEs)
• 10.7% of hospital admissions in older adults
• “If medication related problems were ranked
as a disease, it would be the fifth leading
cause of death in the US!”
Kongkaew C, et al. Annals of Pharmacotherapy 2008; 42:1017-1025
Budnitz et al. N Engl J Med 2011;365:2000-12.
Beers MH. Arch Internal Med. 2003
Pharmacokinetics Change with Age
• Absorption
– Other drugs, nutrition, gastric emptying
• Distribution
– ↑adipose/↓lean, water
• Binding/Localization
– ↓albumin
• Biotransformation
– ↓Hepatic Clearance (some drugs), great variability
• Elimination
– ↓GFR
…and diminished homeostatic reserve
Need for Balance
Risk…
Rane A, Lindh JD. Hum Genomics Proteomics 2010
…mitigated by other meds….
Rane A, Lindh JD. Hum Genomics Proteomics 2010
Need for Balance
Benefit…
Rane A, Lindh JD. Hum Genomics Proteomics 2010
Need for Balance
Benefit…all of it!
Rane A, Lindh JD. Hum Genomics Proteomics 2010
% event-free
Need for Balance
Is the effect
statistically and/or
clinically significant?
TIME
Is there a wide variation in time to
benefit, or by subgroups?
Diabetes Mellitus
• Less stringent control reasonable in those
with a long history of diabetes, limited life
expectancy, or comorbid conditions

ADA Standards of Medical Care in Diabetes 2012.
Sjoblom P. Diabetes Res Clin Prac 2008; 82:197-202.
Drug withdrawal
study in 17 nursing
homes in patients
with HbA1c <6:
safe to discontinue
all oral meds, and
stop or reduce
insulin
Top Five Problematic
Medication Classes leading to ED
1.
2.
3.
4.
5.
Oral Hypoglycemic
15.0%
Hematologic
67%
Endocrine agents
18.7%
Cardiovascular agents
19.5%
Central Nervous System Agents
Anti-infective
Oral Antiplatelet
46.8%
Warfarin
Insulin
Budnitz et al. N Engl J Med 2011;365:2000-12.2
…including time to benefit
Proportion in the PROSPER Trial with CHD
Death, Non-Fatal MI, or Stroke
PROSPER. Lancet 2002; 360: 1623–30.
Osteoporosis
% fracture-free
bisphosphonate
Prevention of
osteoporotic
fracture
50% reduction in risk
of fracture over a 3
year period
1.2% absolute risk
reduction for fractures
in 3 years
placebo
Time to benefit
9 to 18 mos
TIME
National Osteoporosis Foundation. Clinician’s guide
to prevention and treatment of osteoporosis, 2009
Median life expectancy:
2.7- 4.7 years
Benefits possibly similar in men,
but data is extrapolated from
studies of women
No “best” approach to either
communicate prognosis nor effect
“optimal” clinical decision making




Guidelines lack adequate ways to
assess prognosis
Published prognosis measures have
limited generalizability
Overwhelming to evaluate prognosis
Uncertainty in how to use prognostic
measures in clinical practice
Consider patient preferences…
• Influenced by the way risk
information is presented to the
patient
• Multimorbidity patients face more
preference-based and complex
decisions
• Eliciting preferences may make
clinical management more timeconsuming
…and patient capabilities
Medication Management Capacity
Drug Regimen Unassisted Grading Scale (DRUGS)
 Edelberg HK, Shallenberger E, Wei JY. Medication management capacity
in highly functioning community-living older adults: detection of early
deficits. J Am Geriatr Soc. 1999 May;47(5):592-6.
Hopkins Medication Schedule (HMS)
 Carlson MC, Fried, LP, Xue QL, et al. Validation of the Hopkins Medication
Schedule to Identify Difficulties in Taking Medications Journal of
Gerontology: Feb 2005;60A,2: Health Module 217-223
Medication Management Instrument for
Deficiencies in the Elderly (MedMaIDE)
 Orwig D, Brandt N, Gruber-Baldini, A. Medication Management
Assessment for Older Adults in the Community. The Gerontologist
2006;46:661-668
PUTTING IT ALL TOGETHER…
Inappropriate Prescribing
Methods to Look at Inappropriate Prescribing
e.g.:
– American Geriatrics Society 2012 Beer’s Criteria
– STOPP (Screening Tool of Older Persons’
potentially inappropriate Prescriptions)
– START (Screening Tool to Alert doctors to the Right
Treatment)
– Clinical Judgment
Hamilton HJ. Inappropriate Prescribing and adverse drug events in older people. BMJ Geriatrics (2009).
Accessed at www.biomedcentral.com/1471-2318/9/5
Bergert FW, Conrad D, Ehrenthal EJ et al. Pharmacotherapy Guidelines for the aged by family doctors for the use
of family doctors. Inter J Clin Pharm Ther (2008) 46:600-616.
HISTORY AND DEVELOPMENT OF
THE AGS 2012 BEERS CRITERIA
Mark H Beers, MD
1954-2009
“ A ballet-dancing opera critic who
hiked the Alps and took up rowing
after diabetes cost him his legs”
•MD, University of Vermont
•First medical student to do a
geriatrics elective at Harvard‘s new
Division on Aging
•Geriatric Fellowship, Harvard
•Faculty, UCLA/RAND
•Co-editor, Merck Manual of Geriatrics
•Editor in Chief, Merck Manuals
Beers Criteria: History and Utilization
• Original 1991 – Nursing home pts
• Updates
– 1997: All elderly; adopted by CMS in 1999
for nursing home regulation
– 2003: Era of generalization to Med D, then
NCQA, HEDIS
– 2012: Further adoption into quality
measures
Specific Aims AGS 2012 Beers Criteria
Specific aim – update 2003 Beers Criteria using a
comprehensive, systematic review and grading of evidence
Strategy:
1. Incorporate new evidence
2. Grade the evidence
3. Use an interdisciplinary panel
4. Incorporate exceptions
Method
Framework
• Expert panel
– 11 members
• IOM 2011 report on guideline development
– Includes a period for public comment
• Literature search
Panel Members
• Co-chairs
– Donna Fick, PhD
– Todd Semla, MS, PharmD
• Panelists (voting)
–
–
–
–
–
–
–
–
–
Judith Beizer, PharmD
Nicole Brandt, PharmD
Catherine DuBeau, MD
Nina Flanagan, CRNP,CS-BC
Joseph Hanlon, PharmD, MS
Peter Hollmann, MD
Sunny Linnebur, PharmD
Stinderpal Sandhu, MD
Michael Steinman, MD
• Nonvoting Panelists
– Robert Dombrowski, PharmD
(CMS)
– David Nau, PhD (PQA)
– Bob Rehm (NCQA)
• AGS Staff
– Christine Campenelli
– Elvy Ickowicz, MPH
• Others
– Sue Radcliff (research)
– Susan Aiello, DVM (editing)
Method
• Literature search: ADE, inappropriate drug use, med
errors, polypharmacy x age/human/English
25,549 citations 12/1/2001 – 3/30/2011
19,044 excluded
6,505 prelim review
4238 excluded
2,267 reviewed by co-chairs
Additional searches, additions
844 excluded
2169 reviewed
Additional searches, additions
258 included in evidence tables
Method
• Survey to panel to rate (strong agreestrong
disagree)
– 2003 Beers meds
– New additions
• Ratings tallied, shared with panel, 2 rounds of
consensus
• In-person: review survey draft and lit search
• 4 groups reviewed lit, selected citations
• Evidence tables prepared, rated quality of evidence
and strength of recommendation
• Final group consensus
Designations of Quality and Strength of Evidence: ACP
Guideline Grading System, GRADE
Quality
•
High Evidence
– Consistent results from well-designed, well-conducted studies that directly assess effects on
health outcomes (2 consistent, higher-quality RCTs or multiple, consistent observational studies
with no significant methodological flaws showing large effects)
•
Moderate Evidence
– Sufficient to determine effects on health outcomes, but the number, quality, size, or consistency
of included studies, generalizability, indirect nature of the evidence on health outcomes (1
higher-quality trial with > 100 participants; 2 higher-quality trials with some inconsistency, or 2
consistent, lower-quality trials; or multiple, consistent observational studies with no significant
methodological flaws showing at least moderate effects) limits the strength of the evidence
•
Low Evidence
–
Insufficient to assess effects on health outcomes because of limited number or power of
studies, large and unexplained inconsistency between higher-quality studies; important flaws in
design or conduct, gaps in the chain of evidence
– Or lack of information on important health outcomes
Designations of Quality and Strength of Evidence:
ACP Guideline Grading System, GRADE
Strength of recommendation
• Strong:
– Benefits clearly > risks and burden OR risks and burden clearly > benefits
• Weak:
– Benefits finely balanced with risks and burden
• Insufficient:
– Insufficient evidence to determine net benefits or risks
AGS 2012 BEERS CRITERIA
CLINICAL HIGHLIGHTS & EVIDENCE
Need for Updates or New Criteria
•Continuous arrivals of new drugs on the market1
•Older formulations unavailable in European formularies2
•Only 12-21% of the medications identified are being used
by older adults3
•Tangible benefit to patients in terms of clinical outcomes2
Fick D, Cooper J, Wade W, et al. Arch Intern Med 2003;163:2716-2724 1
Hamilton H, Gallagher P, Ryan C, Arch Intern Med 2011;171(11):1013-1019 2
Rudolph J, Salow M, Angelini M et al. Arch Inern Med 2008; 168 (5): 508-513 3
Beers Criteria- 3 Main Tables
1) Table 2: Medications or medication classes
that should be avoided in persons 65 years or
older
1) Table 3: Medications that should not be used
in older person known to have specific
medical diseases or conditions.
1) Table 4: Medications that should be used
with caution
Beers Criteria: Overall Results
• A total of 53 medications or medication
classes, which are divided into three tables.
• Constructed and organized by:
– major therapeutic classes and
– organ systems
Beers Criteria: Table 2 Results
– 34 potentially inappropriate
medications/classes to avoid in older adults
independent of diagnoses or conditions.
– Notable mentions:
–Sliding Scale Insulin
–Antipsychotics for Behavioral Health
issues associated with dementia
–Non benzodiazepine Hypnotics
–Megestrol
Sliding Scale
Organ
Rationale
System/
Therapeutic
Category/D
rug(s)
Insulin,
Higher risk of
sliding scale hypoglycemia
without
improvement in
hyperglycemia
management
regardless of
care setting.
Recom Quality of
mendati Evidence
on
Strength of References
Recommen
dation
Avoid
Strong
Moderate
Queale
1997
Important to look at during transitions in care due to the fact that
PO Diabetes meds are stopped when they are admitted and
typically have insulin protocols in place.
Antipsychotics
Organ
System/
Therapeuti
c
Category/D
rug(s)
Antipsychot
ics, first(convention
al) and
second(atypical)
generation
(see Table 8
for full list)
Rationale
Recommendatio Quality Strength References
n
of
of
Evidenc Recomm
e
endation
Increased Avoid use for
Modera Strong
Dore 2009
risk of
behavioral
te
Maher
cerebrovas problems of
2011
cular
dementia unless
Schneider
accident
non2005
(stroke)
pharmacologic
Schneider
and
options have
2006a
mortality in failed and patient
Schneider
persons
is threat to self or
2006b
withaddition others.
Timely
with the increased focus on safety andVigen 2011
dementia.
efficacy
in patients on these medications especially within
the nursing home setting.
Non Benzodiazepine Hypnotics
Organ
System/
Therapeutic
Category/D
rug(s)
Nonbenzodi
azepine
hypnotics
Eszopiclone
Zolpidem
Zaleplon
Rationale
Recomme Quality of
ndation
Evidence
Strength References
of
Recomm
endation
Benzodiazepinereceptor agonists
that have adverse
events similar to
those of
benzodiazepines in
older adults (e.g.,
delirium, falls,
fractures); minimal
improvement in
sleep latency and
duration.
Avoid
chronic
use (>90
days)
Strong
Moderate
Allain 2005
Cotroneo
2007
Finkle 2011
McCrae
2007
Orriols 2011
Rhalimi
2009
Megestrol
Organ
Rationale
Recomm Quality
System/
endation of
Therapeuti
Evidence
c
Category/D
rug(s)
Megestrol Minimal effect on Avoid
Moderat
weight; increases
e
risk of thrombotic
events and
possibly death in
older adults.
Strength
References
of
Recomme
ndation
Strong
Bodenner
2007
Reuben
2005
Simmons
2005
Yeh 2000
Beers Criteria: Table 3 Notables
Disease/Syndrome
Heart failure
Syncope
Drug/Drug Class
NSAIDs and COX-2
inhibitors
Nondihydropyridine CCBs
(avoid only for systolic
heart failure)
Diltiazem
Verapamil
Pioglitazone,
rosiglitazone
Cilostazol
Dronedarone
Acetylcholinesterase
inhibitors (CEIs)
Peripheral alpha blockers
Tertiary TCAs
Chlorpromazine,
thioridazine, and
Rationale
Potential to promote fluid
retention and/or
exacerbate heart failure
Increases risk of orthostatic
hypotension or bradycardia
Beers Criteria: Table 3 Notables
Disease/Syndr
ome
Drug/Drug Class
Rationale
History of falls
or fractures
Anticonvulsants
Antipsychotics
Benzodiazepines
Nonbenzodiazepine hypnotics
Eszopiclone
Zaleplon
Zolpidem
TCAs and SSRIs
Ability to produce ataxia,
impaired psychomotor
function, syncope, and
additional falls; shorteracting benzodiazepines are
not safer than long-acting
ones
Delirium
All TCAs
Anticholinergics
Benzodiazepines
Chlorpromazine
Corticosteroids
H2r receptor antagonists.
Meperidine
Sedative hypnotics
Thioridazine
Avoid in older adults with or at
high risk of delirium because of
inducing or worsening delirium
in older adults; if discontinuing
drugs used chronically, taper to
avoid withdrawal symptoms.
Beers Criteria: Table 4 Notable Mentions
Drug
Rationale
Recommendation
ASA for Primary Prevention of
cardiac events
 Antipsychotics
 Carbamazepine
 Carboplatin
 Chlorpropamide
 Cisplatin
 Mirtazapine
 SNRIs
 SSRIs
 TCAs
 Vincristine
Limited data in individuals > 80 Use with caution in adults > 80
May exacerbate or cause
Use with caution
SIADH or hyponatremia; need
to monitor sodium level closely
when starting or changing
dosages in older adults due to
increased risk
Limitations
• Older adults often under-represented in drug
trials potentially underestimating medication
related problems/evidence grading.
• Does not comprehensively address the needs
of palliative and hospice care patients
• Does not address other types of potential
potentially inappropriate medications
– e.g.:
• dosing of primarily renally eliminated medications,
• drug-drug- interactions
Take Home Points
• This is just one tool that
can be utilized to
optimize medication
management in older
adults.
• Need to make sure the
Beers list is used in a
patient centered
manner
Resources Available Online
www.americangeriatrics.org
For the Health Professional
• Downloadable pocket card
• Evidence tables with links to supporting
references
• Beers app – AGS iGeriatrics
For the Layperson
• Summary in lay language
• Q & A on what to do if one of your drugs is on the
Beers list
• Medication diary & tips for safe use of meds
Evidence Tables
Patient Education
Beers Criteria only Part of Quality Prescribing
Quality prescribing includes:
• Correct drug for correct diagnosis
• Appropriate dose (label; dose adjustments
for co-morbidity, drug-drug interactions)
• Avoiding underuse of potentially important
medications (e.g., bisphosphonates for
osteoporosis)
• Avoiding overuse (e.g., antibiotics)
• Avoiding potentially inappropriate drugs
• Avoiding withdrawal effects with
discontinuation
• Consideration of cost
The Enhanced Monitoring Framework
Primary Concern
Patient Education and
Activation
Complete Review
Including meds
Educate and activate patient to
understand and report medrelated problems
?Interactions
Initial
prescribing
decision
?benefits/harms
Evidence and guidelines
Prognosis
Follow-up Prescribing
Decision
-Maintain drug
-Change dose, frequency,
form
-Discontinue
-Substitute
-Add new drug
Monitor
-Side effects, effectiveness
and adherence
-Assess if med still needed
Patient preference and feasibility
Modified from: Steinman MA et al. Beyond the prescription: Medication monitoring and adverse drug events in
older adults. JAGS. 2011;59(1):1513-20.
Why is this important?
• Quality Metrics
– HEDIS:
http://www.ncqa.org/HEDISQualityMeasurement/
HEDISMeasures/HEDIS2013/HEDIS2013FinalNDCLi
sts.aspx
• Improved patient care
• Decrease liability
Take Home Points
• Medication Management
& Monitoring takes a
team!
• It needs to be patient
centered.
• Most importantly,
monitoring needs to be
evaluated on an ongoing
basis.